Loading…
Epigenetic addition of m5C to HBV transcripts promotes viral replication and evasion of innate antiviral responses
Eukaryotic five-methylcytosine (m 5 C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m 5 C sites are identified in hepatitis B virus (HBV) mRNA. The m 5 C modification at nt 1291 is...
Saved in:
Published in: | Cell death & disease 2024-01, Vol.15 (1), p.39-39, Article 39 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Eukaryotic five-methylcytosine (m
5
C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m
5
C sites are identified in hepatitis B virus (HBV) mRNA. The m
5
C modification at nt 1291 is not only indispensable for Aly/REF export factor (ALYREF) recognition to promote viral mRNA export and HBx translation but also for the inhibition of RIG-I binding to suppress interferon-β (IFN-β) production. Moreover, NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the addition of m
5
C to HBV mRNA and is transcriptionally downregulated by the viral protein HBx, which suppresses the binding of EGR1 to the NSUN2 promoter. Additionally, NSUN2 expression correlates with m
5
C modification of type I IFN mRNA in host cells, thus, positively regulating IFN expression. Hence, the delicate regulation of NSUN2 expression induces m
5
C modification of HBV mRNA while decreasing the levels of m
5
C in host IFN mRNA, making it a vital component of the HBV life cycle. These findings provide new molecular insights into the mechanism of HBV-mediated IFN inhibition and may inform the development of new IFN-α based therapies. |
---|---|
ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-023-06412-9 |